Evaluating XMRV As An Indicator Of Prostate Cancer Risk

I found this through Google. Not sure if this should have been published yet as it is a thesis with the date of august 2011 on it? Maybe a mod can be the judge on this and move it to a private section if deemed more apprioriate...

Full PDF is linked on the page below.

Degree
MS, Kent State University, College of Arts and Sciences / School of Biomedical Sciences, 2011.

Abstract
Xenotropic Murine Leukemia Virus-Related Virus (XMRV) is a retrovirus originally identified in human prostate cancer tissues. Different studies show large differences in the detection of XMRV in prostate cancer patients (0 to 27%). While the explanation for this variability is unknown, genetics, geographical distribution, sequence diversity in viral strains, methodological variations and laboratory contamination are suspected.

Here we will describe our methods for detecting low copies of XMRV nucleic acids in urine. Urine specimens from cancer patients are sometimes used as a source of RNA for monitoring expression of genes of interest, such as genes implicated in oncogenesis and metastasis.

RNA was extracted from urine samples and real-time RT - PCR was used to measure low copies of XMRV RNA. Confirmation of the presence of XMRV nucleic acids was obtained by nested RT - PCR. These methods specifically amplify env sequences corresponding to variable regions A and C of the gp70 envelope protein. The amplicons were sequenced and matched to previously published XMRV sequences. The low levels of XMRV nucleic acids in patient samples highlight the challenges of performing PCR methods as an indicator of XMRV infections. However, in the future, high throughput automated PCR methods may lead to large-scale screening of prostate cancer patients. Such methods have the potential to be a convenient assay on a readily obtainable body fluid like urine.

Both assays were able to detect extremely small levels of mouse RNA or DNA (Fig. 3.6). However, neither mouse DNA or RNA was detected in any of the prostate cancer urine samples which had previously tested positive for XMRV (Table 3.3) suggesting the absence of contamination in our samples due to mouse sources.

True, though my respect for the peer review system has been lessened somewhat the last couple of years...

Click to expand...

lol - something of an understatement?

Only partially related to this thread... if someone had been working on a PHD on XMRV for years, and then just before it was completed it turned out that XMRV was a contaminant which they hadn't effectively controlled for, would they have to start all over again? Silverman's been working on XMRV for ages - if it does turn out that his work is the result of contamination, is he going to have students who whose work becomes indefensible prior to it being assessed? Or do they have some system for judging the remainder of the work anyway? Anyone know?

Since this is not about ME/CFS it might attract a bit less fire I think Frank Ruscetti has been working on similar methods. It's good to see that research into XMRV is continuing. I wonder if in cases of ME/CFS XMRV can also be found in this way, or if these (ME/CFS) are the cases where XMRV does not go to the prostate but more to another place (brain, gut, whatever). I'm only speculating of course.

True, though my respect for the peer review system has been lessened somewhat the last couple of years...

Click to expand...

Well as the saying goes, it's the least bad system we've got (like deomcracy). The good thing about the system is that eventually a concensus is reached and fraud or erroneous results that can't be replicated are identified. It takes time but it works in the end. HIV as the cause of AIDS, Margulis' theory of endosymbiosis, the bacterial cause of stomach ulcers are all examples of paradigm shifting work that took time and evidence to be acepted.

I think I'd prefer the end of peer-review. It ends up giving unwarranted respectability to poor papers.

I'd rather have every paper viewed with instinctive scepticism, and researchers required to put much more extensive information about their work up on-line along with publication of their work.

Some journal's now let you view the peer review process - and that's a good move in the right direction because it shows people just how shoddy the process itself is, hopefully making it harder for people to trust work just because it got through peer review. It could also be that my perspective on this matters is unduly influenced by my interest in CFS, which suffers a great deal from poor papers getting past peer review and then being used to justify all sorts of harmful behaviour.

If we want to be able to talk about 'peer reviewed papers' in the way that many do, as if this is a sign of respectable scholarship, then a lot more time and money needs to be devoted to ensuring papers are reviewed thoroughly.

I think I'd prefer the end of peer-review. It ends up giving unwarranted respectability to poor papers.

Click to expand...

That's why Journals have impact rating, poor reviewing usually goes with poor journals. Haven't you ever had your work reviewed by a really good journal? In my experience you have to justify every word and every experiment, they tear your work apart.

I'd rather have every paper viewed with instinctive scepticism, and researchers required to put much more extensive information about their work up on-line along with publication of their work.

Click to expand...

All new work IS viewed with scepticism, most people I know assume everything in Nature and Science is wrong until it's replicated by other labs. And most decent journals allow you to submit all your data along with what's going into the paper. I'm in the process at the moment and I'm going to submit the raw data from every experiment.

Some journal's now let you view the peer review process

Click to expand...

As far as I know they all do, you get the reviewer's comments back from them . Anyway, the alternative is much work, if you want to see a non peer reviewed journal have a look at Medical Hypotheses.

There is nothing majorly wrong with peer-review. The only mistake is to assume that the peer-review that takes place before publishing is the end of the peer-review. It is not the end, but rather the start..

There is nothing majorly wrong with peer-review. The only mistake is to assume that the peer-review that takes place before publishing is the end of the peer-review. It is not the end, but rather the start..

Click to expand...

That should be true....

but for backwater areas of research like CFS, particularly when only a handful of researcher will be interested in each particular aspect of the illness, there's often no real follow-up by critics/sceptics of a particular paper.

Peer review works well in a lot of areas of science, but even there I think it would be better if the process were more consistently laid bare. For work on the edges of science, or where there is little funding/interest, I think that the implied prestige of peer review can do more harm than good.

I agree that there is probably no better alternative available, but to be honest, at this moment, i think a MSc thesis with the name Silverman on it means more than a peer-reviewed article authored and reviewed by some of the usual suspects we talk about on here (those who are not able to find anything anywhere and thus assume it doesn't exist outside of a lab).

The people you know probably don't work with CFS patients then, at least not in the UK... or maybe they're some of the very rare good ones.

Click to expand...

Eh? You do know that the Lombardi paper was published in Science? Are you agreeing that scientsts should be sceptical about it until it's findings are replicated? Which papers on the subject do you think aren't well peer reviewed and why?

There is nothing majorly wrong with peer-review. The only mistake is to assume that the peer-review that takes place before publishing is the end of the peer-review. It is not the end, but rather the start..

Peer review works well in a lot of areas of science, but even there I think it would be better if the process were more consistently laid bare. For work on the edges of science, or where there is little funding/interest, I think that the implied prestige of peer review can do more harm than good.

Eh? You do know that the Lombardi paper was published in Science? Are you agreeing that scientsts should be sceptical about it until it's findings are replicated? Which papers on the subject do you think aren't well peer reviewed and why?

Click to expand...

Yeah, I had noticed that it was published in Science. Of course scientists should be sceptical of it until it is replicated. Why are you asking?

Both of these two are good examples of my point - rather poor work is published, and then media and other organisations report whatever spin the researchers put upon them without any real critical analysis because they think that the peer review process absolves them of that responsibility, so that instead of an on-going process of sceptical assessment, we have a process in which unfounded claims are exaggerated and repeated as they are passed on to doctors/patients/etc.

I'm far from committed in my preference for an overhaul of the peer-review process, but these are the problems I have with it, and why I think it can do more harm than good.

But i think there are some things you can't lay bare, like the identity of the reviewers, or do they do that? Because that would probably create a lot of trouble.

Click to expand...

Actually - I was reading some peer review stuff that did include the identity of the reviewers. It was really helpful to see, as the peer reviewers were really disagreeing amongst themselves about the quality of the paper, and you could see that this clearly related to their own beliefs about CFS. Seeing as CFS is often more about ideology and politics than the evidence, knowing who the peer reviewers are can be a better guide to whether they will approve of a paper that the quality of the research itself.

Right, I thought you were talking about XMRV research given that this forum is specifically about XMRV. I work in the molecular sciences so I couldn't possibly comment on the peer review process of any other field.

I had made it clear that my concerns focused upon the edges of science, or areas where there is less interest/funding.

You could possibly comment upon the peer review process of other fields if you took some time to read and think about it; that so many feel instinctively unwilling to do so is one of the problems with it.